Unravelling the mysteries of sudden unexpected death in epilepsy. / Desentrañando los misterios de la muerte súbita en epilepsia.

INTRODUCTION: Sudden unexpected death in epilepsy (SUDEP) is the most frequent cause of premature death in epileptic patients. Most SUDEP events occur at night and frequently go unnoticed; the exact pathophysiological mechanisms of this phenomenon therefore remain undetermined. Nevertheless, most cases of SUDEP are attributed to an infrequent yet extremely severe complication of epileptic seizures. DEVELOPMENT: We conducted a systematic literature search on PubMed. Our review article summarises scientific evidence on the classification, pathophysiological mechanisms, risk factors, biomarkers, and prevention of SUDEP. Likewise, we propose new lines of research and critically analyse findings that are relevant to clinical practice. CONCLUSIONS: Current knowledge suggests that SUDEP is a heterogeneous phenomenon caused by multiple factors. In most cases, however, SUDEP is thought to be due to postictal cardiorespiratory failure triggered by generalised tonic-clonic seizures and ultimately leading to cardiac arrest. The underlying pathophysiological mechanism involves multiple factors, ranging from genetic predisposition to environmental factors. Risk of SUDEP is higher in young adults with uncontrolled generalised tonic-clonic seizures. However, patients apparently at lower risk may also experience SUDEP. Current research focuses on identifying genetic and neuroimaging biomarkers that may help determine which patients are at high risk for SUDEP. Antiepileptic treatment is the only preventive measure proven effective to date. Night-time monitoring together with early resuscitation may reduce the risk of SUDEP.

Gait instability in valproate-treated patients: Call to measure ammonia levels.

OBJECTIVE: Hyperammonemia induced by valproate (VPA) treatment may lead to several neurological and systemic symptoms as well as to seizure exacerbation. Gait instability and recurrent falls are rarely mentioned as symptoms, especially not as predominant ones. METHODS: We report five adult patients with frontal lobe epilepsy (FLE) who were treated with VPA and in whom a primary adverse effect was unstable gait and falls. RESULTS: There were four males and one female patients with FLE, 25-42-year-old, three following epilepsy surgery. All of them were treated with antiepileptic drug polytherapy. Gait instability with falls was one of the principal sequelae of the treatment. Patients also exhibited mild encephalopathy (all patients) and flapping tremor (three patients) that developed following the addition of VPA (three patients) and with chronic VPA treatment (two patients). VPA levels were within the reference range. Serum ammonia levels were significantly elevated (291-407 µmole/L, normal 20-85) with normal or slightly elevated liver enzymes. VPA dose reduction or discontinuation led to the return of ammonia levels to normal and resolution of the clinical symptoms, including seizures, which disappeared in two patients and either decreased in frequency or became shorter in duration in the other three. CONCLUSIONS: Gait instability due to hyperammonemia and VPA treatment is probably under-recognized in many patients. It can develop when the VPA levels are within the reference range and with normal or slightly elevated liver enzymes.

Rasmussen encephalitis with ipsilateral brain stem involvement in an adult patient.

Rasmussen encephalitis is a rare unihemispheric inflammatory disease of the brain that leads to intractable seizures, cognitive decline and progressive neurological deficits associated with the affected hemisphere. It predominantly affects children, with the onset in adults having a milder course. Here the case of an adult woman with Rasmussen encephalitis responsive to immunosupression is reported.

[Transcranial Doppler velocimeter in pregnant and later normotensive puerperal women]. / Velocimetría Doppler transcraneal en gestantes y posteriormente puérperas normotensas.

INTRODUCTION: The physiological changes that take place in blood flow in the brain during pregnancy and the puerperium are still only poorly understood. The harmlessness of transcranial Doppler (TCD) makes it a suitable method of study. AIMS: The purpose of this study was to determine the TCD velocimeter reading at the end of pregnancy and in the early puerperium of healthy expectant mothers. SUBJECTS AND METHODS: TCD was used to perform a bilateral study of the anterior (ACA), middle (MCA) and posterior cerebral arteries (PCA). Arterial blood pressure and haematocrit were also measured. Mean velocity (MV), the pulsatility index (PI), mean arterial blood pressure and haematocrit were employed as variables in the statistical analysis. Results from 44 normotensive pregnant women in the latter stages of gestation (week 33 to term) were compared with those of a control group made up of 58 women of a similar age, who were normotensive and not pregnant. The study was repeated in the group of pregnant women during the early puerperium (the first five days after labour) and the two different results were compared. RESULTS: Age and MAP were similar in the gestating and non-gestating groups. Haematocrit was significantly lower in the former (p < 0.001) and MV were significantly lower in the pregnant women in all the arteries (p < 0.001), whereas the PI were also significantly lower in four of the six territories that were studied (p < 0.005). During the puerperium, a significant rise in MV was observed in all the arteries (p < 0.001) and the PI increased in three of them (p < 0.05). In this phase, the mean arterial pressure rose (p < 0.05), although haematocrit levels dropped (p < 0.001). CONCLUSIONS: The low MV and PI seen at the end of pregnancy are compatible with cerebral vasodilatation. MV increase during the early puerperium and is probably linked to a relative hyperperfusion.

[Anomalies in brain haemodynamics in pre-eclamptic expectant mothers]. / Anomalías hemodinámicas cerebrales en gestantes con preeclampsia.

INTRODUCTION: Transcranial Doppler (TCD) is being used more and more frequently in the study of brain haemodynamics in pre-eclampsia/eclampsia. It has received less attention in the puerperium of these patients. AIMS: The aim of our study was to compare pre-eclamptic (PE) and normotensive (NT) patients at the end of gestation, using a Doppler velocimeter, and also to compare the results from PE women in two consecutive periods of time: at the end of gestation and in early puerperium (EP). PATIENTS AND METHODS: TCD was performed with bilateral evaluation of the anterior, middle and posterior cerebral arteries (ACA, MCA and PCA, respectively). Average speed (AS) and the pulsatility index (PI) were used as Doppler parameters. Arterial blood pressure (BP) and haematocrit were also measured. The AS, PI, average BP (ABP) and haematocrit were used as variables in the statistical analysis. At the end of gestation (33 weeks to full term) we compared the average values of these variables in PE (n=38) against those of NT (n=44). We also compared the results obtained for PE (n=30) in two consecutive periods: at the end of gestation and EP (the first five days following childbirth). RESULTS: At the end of gestation, AS were significantly higher in the PE than in the NT in all the arteries that were examined. The ABP was higher in the first group but there was no significant correlation between ABP and AS. PI were lower in the first group, with statistical signification in four of the six arteries. The AS rose significantly in the EP of the PE women, in spite of the existence of a drop in the ABP. Conversely, the PI remained unaltered. CONCLUSIONS: A pattern of high AS and low PI was found in PE women at the end of gestation and may be due to a primary failure of the brain's capacity to regulate itself. Anomalies in the TCD increased in the EP, despite a drop in the ABP, and this could account for the predominance of the neurological symptoms that are reported in the later forms of the syndrome.